Synthesis of the mammalian metabolites of dibenz[a,j]anthracene: dibenz[a,j]anthracene 3,4-oxide and (–)-(3R,4R)-trans-3,4-dihydroxy-3,4-dihydrodibenz[a,j]anthracene

Abstract

Dibenz[a,j]anthracene 3,4-oxide (2) and the isomeric oxepine (19) were synthesised simultaneously from a common dibromoester precursor (9). The oxepine isomer (19) was also formed by photoisomerisation of the arene oxide (2). Resolution and absolute configuration assignment of each enantiomer of trans-3-bromo-4-hydroxy-1,2,3,4-tetrahydrodibenz[a,j]anthracene (10) was achieved by chromatographic separation and recrystallisation of the MTPA diastereoisomers (11a/11b). The (+)-(3S, 4S)bromo-MTPA ester (11a) was used in a seven-step synthesis of the chiral metabolite (–)-(3R, 4R)-trans-3,4-dihydroxy-3,4-dihydrodibenz[a,j]anthracene (3). The (–)-(3R, 4R)-bromo-MTPA ester diastereoisomer (11b) similarly served as a precursor of (3S, 4R)-dibenz[a,j] anthracene 3,4-oxide (2) which spontaneously racemised via an unstable oxepine isomer (18).